This Competing Continuation Application for a well-established Ruth L. Kirschstein Institutional National Research Service Award (T32) is focused on the postdoctoral training of M.D., M.D.-Ph.D., and Ph.D. candidates to prepare them to pursue independent careers as successful Clinician-Scientists and/or Biomedical Research Scientists, whose primary interest is the cellular and molecular mechanisms of human disease. Its primary training goal is the development of core research competencies through both informal and structured didactic exercises, coupled with an in-depth mentored research experience, in a nurturing and supportive academic medical center environment. The programmatic emphasis is on understanding the basic pathogenetic mechanisms underlying major disease processes that affect the cardiovascular, pulmonary, hematopoietic and immune systems, through the application of the multidisciplinary research tools and strategies of modern cellular and molecular biology, immunology, genetics and genomics, integrative physiology and bioinformatics. The current Training Program, sponsored by the National Heart, Lung and Blood Institute, has been in continuous existence since 1958, and is based in the Department of Pathology at the Brigham and Women's Hospital, a primary teaching affiliate of Harvard Medical School. While the Training Program's Core Faculty is comprised primarily of clinician-scientists and basic biomedical researchers in the Department of Pathology, trainees also are encouraged to avail themselves of a wide spectrum of opportunities afforded by research mentors/laboratories in Harvard-affiliated research/medical center institutions (e.g., The Immune Diseases Institute - formerly the Center for Blood Research, the Broad Institute, Children's Hospital Boston, Massachusetts General Hospital, Massachusetts Institute of Technology and Dana-Farber Cancer Institute). Trainees are selected from a national pool of applicants, via a proactive recruitment process, and the Program's emphasis is on tailoring a research training experience to fit a given candidate's background, scientific interests and career goals. The overarching scientific principle is one of translational molecular pathology - the probing of disease mechanisms at a fundamental mechanistic level that yields new insights that point the way to targeted treatments for diseases, and, ultimately, their prevention. RELEVANCE (See instructions): Diseases of the cardiovascular system (e.g., heart attacks and strokes), as well as disorders of the blood and immune systems (e.g., autoimmune disorders) represent a major health burden. Equipped with the skills of modern molecular pathology, new researchers can learn to probe the basic mechanisms of these diverse diseases and then translate this knowledge into novel and effective treatments and preventative measures.